L33 Breast Pathology Part II - Malignancy onwards Flashcards
What are the genetic changes related to Familial Brest carcinoma (10%) ? (4)
- BRCA1/2 (tumor suppressor gene)
- AD inheritance with variable penetrance
- TP53 germline mutation
- PTEN mutation (Cowden syndrome/ multiple harmatoma syndrome - Benign overgrowths called hamartomas as well as an increased lifetime risk of breast, thyroid, uterine, and other cancers.)
AD inheritance cause of familial breast carcinoma is associated with triple-ve Ca breast, Ca ovary and CA male breast.
What does it meant by triple -ve ?
Potential treatment?
Negativity for ER,PR and HER2
Tx: PARP1 inhibitor
Which of the following regarding malignant breast tumors are correct?
A. Family history would cause a 50% increase in risk of malignancy
B. American black females are prone to have a younger onset and higher grade
C. Malignancy is rare before 25 years old and has a steady increase until 65
D. Late menarche is a risk factor
E. Age of having the first child >30 causes an increase risk.
All except D
D: Early menarche and Late menopause = increased estrogen exposure
Risks of CA breast related to oestrogen exposure?
other than early menarche, late menopause, age of having 1st child
- Parity - uninterrupted menstrual cycle (interrupted = abortion, pregnancy, lactation, reduced breast cancer)
- Obesity in post-menopause: peripheral fat instead of ovary in post-menopause women for oestrogen production
- Proliferative breast lesion: atypical hyperplasia (4x)
- Carcinoma of contralateral breast/endometrium
What is carcinoma in situ?
Malignant cells not yet penetrate the basement membrane (beneath myoepithelial cells)
What are the 2 types of carcinoma in situ of the breast? (2)
Main diference? (2)
- Ductal carcinoma in situ (DCIS)
- Lobular carcinoma in situ (LCIS)
(not staged as CIS but as benign disease in 8th AJCC) - DCIS: malignant cells in the ducts without invasion
- LCIS: malignant cells in the lobules without invasion
( loss of E-cadherin: loose)
What is Comedo DCIS?
What grade does it belong to?
‘Plug’
Breast duct is completely plugged by cancer cells, rapid proliferation of the cell > centre undergoes necrosis.
= High grade
Which of the following regard DCIS and LCIS are incorrect?
A. Both are diagnosed by core biopsy
B. Both are asymptomatic
C. DCIS is palpable while LCIS is not
D. Pleomorphic microcalfications can be seen in mammography of DCIS due to dystrophic calcifications, while no abnormality to LCIS
E. Both can be low grade or high grade
C
- Both impalpable
DCIS: inflammation and fibrosis at the peripheral of cancer > impalpable
LCIS: loose cell arrangement
Why would DCIS and LCIS cause CA risk respectively? (2)
How many percent increase/year?
DCIS
- Precursor to invasive ductal carcinoma of the same breast -1%/year
LCIS
- Precursor and marker of bilateral invasive carcinoma (ductal/lobular) -1%/year
Treatment for DCIS? (3)
- Breast-conservation therapy +/- RT
- Total mastectomy if diffuse breast involvement
- Adjuvant: Tamoxifen (if ER +ve) ( selective estrogen receptor modulator used to prevent breast cancer)
Treatment for LCIS? (3)
- Lifelong close surveillance
- High risk patients: Bilateral total masectomy
- Adjuvant: Tamoxifen if ER+ve
Eczematous changes and crusting exudate of the nipple. Dx? (1)
Pathology?(2)
Paget disease of the nipple
- infiltration of nipple epidermis by malignancy cells
- a/w underlying carcinoma (DCIS/invasive ductal carcinoma)
Name the 2 types of invasive carcinoma of the breast.
- Invasive ductal carcinoma NOS (MC: 80%)
(not otherwise specified = no specific histomorphological feature)
- Invasive lobular carcinoma (<20%)
What are the differences in
1) Presentation
2) Molecular markers
between Invasive ducal VS lobular carcinoma?
1) Presentation
- IDC: palpable firm mass
- ILC: Non-palpable firm mass
2) Molecular markers
- IDC: ER, PR, HER2
- ILC: ER/PR+ with HER2 -ve usually
Pathology of invasive ductal carcinoma? (3)
- Desmoplasic reaction (dense fibrotic) = inflammation + fibrosis
- Hard, retracted apperance
- Invasive nests
Pathology of invasive lobular carcinoma? (3)
- Loss of E-cadherin: bull’s eye pattern (tumor cells surround ducts and lobules)/
loosely arranged in strands/cords/single cell
(when cells arranged in a line> suspect ILC)
Inflammatory and metaplastic histomorphological features in CA breast points to poor prognosis.
How about good prognosis? (4)
- Mucinous
- Tubular
- Secretory
- Adenoid cystic
Which of the following are indicators for therapy choice?
A. Histology
B. Molecular markers
C. Both
D. Neither
B only!
A: only for prognosis
Histological grading of a breast tumor is by looking at? (3)
- Nuclear morphology
- Mitosis
- Tubule formation
How does LN spread in breast tumors?
Axillary >
Internal mammary > Supraclavicular
> Lungs, bone, liver, adrenal
What are sentinel lymph nodes?
How is it identified?
First nodes to which cancer cells may spread from a tumor = axilla.
Best: intra-operatively
1. Injection of methylene blue + radioactive isotope (sulphur colloid) around the tumour
- after 5mins -1hr - 1st excise the 1st draining lymph node (groups)
if -ve sentinel lymph nodes, still require axillary dissection?
No, otherwise may case lymphedema of upper limb/ risk of lymphangiosarcoma
ER/PR+ve means which 2 types ?
Treatment? (2)
Luminal A: LG
Luminal B: HG
Tx:
1. Tamoxifen - SERM (selective estrogen receptor modulator)
- Aromatase inhibitors e.g. anastrozole
(aromatase: testosterone > estrogen)
ER/PR -ve > check for?
Relative prognosis?
HER2 +ve: HG
> poor prognosis, Tx: trastuzumab (Herceptin) (monoclonal antibody)
HER2 -ve = triple
negative: HG (worst prognosis)
> Chemotherapy needed
Proliferative rate is assessed by?
Ki67
Low = Good Px
High = Poor Px > dose dense chemotherapy
Others:
Chromosome aberration in CA breast prognosis?
Diploid = Good Aneuploid = Poor (abnormal number of chromosomes)
Drugs for
- Immunotherapy
- BRCA mutation
- PD-L1 inhibitor
2. PARP inhibitors
Which of the following regarding gene based assays in CA breast is correct?
A. Oncotype Dx: 21 genes for recurrence score for early stage, node -ve, ER+ CA breast
B. Oncotype Dx is predicative for adjuvant chemotherapy
C. Mammaprint is for recurrence of early stage CA breast
D. Prosigna predicts 10 years distant recurrence
E. Calculates recurrence risk and thus therapeutic dose
All of the above
Gynaecomastia in male = fibrocystic change-equivalent in female
Reason? (3)
High estrogen state
- Increase in estrogen
- digoxin
- puberty/old age
- liver failure (stigmata of chronic liver disease) - Decrease in androgen
- leuprolide (Tx for CA prostate) - Defect in androgen receptor
- androgen insensitivity syndrome
- spironolactone
Carcinoma of breast in male
A. 1:100 ratio M:F
B. Presents late
C. Invades early
D. Histology similar to carcinoma in female
E. Extend outside breast even if it is rudimentary (early stage)
All of the above
